Lingzhi an herbal mushroom, used in traditional Chinese medicine for at least 2,000 years, which is a species complex that encompasses several fungal species of the genus Ganoderma, most commonly the closely related species Ganoderma lucidum, Ganoderma tsugae, and Ganoderma sichuanense. Many therapeutic effects have been reported of Lingzhi species, such as immunomodulatory, anti-tumor, hepato-protective, antioxidant, and cholesterol-lowering effects (Jinn et al., 2006, Biosci Biotechnol Biochem, 70, 2627-2634). All of these therapeutic effects are attributed from triterpenoids, polysaccharides, and glycoproteins (Boh et al., 2007, Biotechnol Annu Rev, 13, 265-301; Jinn et al., 2006, Biosci Biotechnol Biochem, 70, 2627-2634). A glycoprotein class in Lingzhi named fungal immunomodulatory proteins (FIPs) was recently identified. So far, at least 5 FIPs have been isolated; i.e., LZ-8, (Ganoderma. lucidum), FIP-gts (Ganoderma tsugae), FIP-gja (Ganoderma sinensis) and GMI (Ganoderma microsporum) (Hsu et al., 1997, Biochem J, 323 (Pt 2), 557-565; Ko et al., 1995, Eur J Biochem, 228, 244-249; Xuanwei et al., 2008, Planta Med, 74, 197-200; and U.S. Pat. No. 7,601,808). According to a previous study, FIP-gts from G. tsugae, a popular chemopreventive mushroom in Asia, has anti-cancer function and is involved in the regulation of hTERT/telomerase expression (Liao et al., 2006, Mol Carcinog, 45, 220-229). In addition, FIP-gts inhibits the growth of A549 cancer cells, leading to cell cycle arrest, consequently inducing premature cellular senescence in lung cancer cells. Moreover, FIP-gts results in significant inhibition of tumor growth in athymic nude mice implanted with A549 cells (Liao et al., 2008, Food Chem Toxicol, 46, 1851-1859). US 20100009915 provides a method for suppressing proliferation of a cancer cell and a method for suppressing a tumor cell mobility, comprising providing to the tumor cell a purified polypeptide of a fungal immunomodulatory protein, LZ-8. U.S. Pat. No. 7,601,808 discloses an immunomodulatory protein cloned from Ganoderma microsporum (i.e., GMI) and this protein has immunomodulator efficiency.
Lung cancer, also known as carcinoma of the lung or pulmonary carcinoma, is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung by process of metastasis into nearby tissue or other parts of the body. The main primary types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC).
Small cell lung cancer (SCLC) accounts for approximately 14% of all lung cancers. Combination chemotherapy is currently considered standard first-line therapy for SCLC. The most common regimens include cisplatin or carboplatin and etoposide. Unfortunately, despite the 40-90% response rate to first-line chemotherapy, long-term survival is unusual because patients develop resistance to chemotherapy and relapse. Non-small cell lung cancer (NSCLC) is a heterogeneous aggregate of histologies, including, e.g., epidermoid or squamous carcinoma, adenocarcinoma, and large cell carcinoma. Patients with NSCLC may be divided into three groups that reflect both the extent of the disease and the treatment approach: (1) patients with tumors that are surgically resectable; (2) patients with either locally or regionally advanced lung cancer; and (3) patients with distant metastases at the time of diagnosis. Current treatments for NSCLC include surgery, chemotherapy, and/or radiation therapy. However, current methods of treating NSCLC are often unsatisfactory, and a need exists for effective therapies to treat subjects with NSCLC.
However, there is no therapy to a refractory or relapsed lung cancer and there is a need to develop an agent as treatment means.